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German Doctor Cures an HIV Patient With a Bone Marrow Transplant 639

Posted by Soulskill
from the not-an-easy-one-though dept.
reporter writes "HIV is the virus that causes Acquired Immune Deficiency Syndrome (AIDS). Until now, HIV has no cure and has led to the deaths of over 25 million people. However, a possible cure has appeared. Dr. Gero Hutter, a brilliant physician in Germany, replaced the bone marrow of an HIV patient with the bone marrow of a donor who has natural immunity to HIV. The new bone marrow in the patient then produced immune-system cells that are immune to HIV. Being unable to hijack any immune cell, the HIV has simply disappeared. The patient has been free of HIV for about 2 years. Some physicians at UCLA have developed a similar therapy and plan to commercialize it."
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German Doctor Cures an HIV Patient With a Bone Marrow Transplant

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  • by Geoffrey.landis (926948) on Sunday November 09, 2008 @12:52PM (#25695001) Homepage
    I'll be really interested to see if this result can be replicated.
    • by Anonymous Coward on Sunday November 09, 2008 @12:57PM (#25695035)

      I'll be really interested to see if this result can be replicated.

      I'll be really interested to see if this DONOR can be replicated.

      • by ScrewMaster (602015) * on Sunday November 09, 2008 @01:02PM (#25695097)

        I'll be really interested to see if this result can be replicated.

        I'll be really interested to see if this DONOR can be replicated.

        I've been expecting something like this ever since the discovery of HIV-immune [wired.com] individuals. So yes, the donor can be replicated.

        • by jcr (53032) <jcr@nOspAm.mac.com> on Sunday November 09, 2008 @01:32PM (#25695353) Journal

          One thing I've been wondering about is whether it would be possible to fight infection just by making a protein that binds to CCR5 and does nothing else. I'm presuming that HIV can't attach to the receptor if there's something in the way.

          Would any molecular biologist reading this please tell me if this works or not?

          -jcr

          • by geckipede (1261408) on Sunday November 09, 2008 @01:42PM (#25695405)
            That's how some of the new drug treatments for HIV work. The article mentions them. Are you suggesting a form of genetic treatment where you don't remove the surface protein from existing cells but add more cells that produce blocking drugs?
            • Re: (Score:3, Interesting)

              by jcr (53032)

              I wasn't suggesting any particular way of administering the blocking proteins, just wondering whether it was a viable strategy.

              -jcr

              • by geckipede (1261408) on Sunday November 09, 2008 @02:00PM (#25695557)
                Most of the drug treatments seemed like a viable strategy at one point. HIV mutates extremely rapidly though, and it seems able to bypass almost anything we can throw at it. If the new types of drugs can reduce the virus's ability to replicate effectively enough that it doesn't get an opportunity evolve a way round then in theory it could work. The problem with that is that you would need to administer the drug reliably on schedule for every infected person all the time and that doesn't happen. The treatments are expensive, and even worse, enough people see HIV/AIDS as some sort of punishment for promiscuity that some people are denied treatments intermittently because people don't feel comfortable giving it to them.
          • by SlashBugs (1339813) on Sunday November 09, 2008 @01:59PM (#25695549)

            Background for non-biologists: HIV typically gains entry to cells by binding two molecules on the healthy cell surface. These are CXCR4 and CCR5. About 1% of white males (other genders/races vary slightly) don't have CCR5; they seem completely healthy and their cells are highly resistant to HIV infection. So blocking the activity of CCR5 seems like an easy way to stop viral infection with no exprected side effects. Tricky to do, but probably worth the effort.

            Anyway, the answer is "yes", sort of. Several antibodies and small peptides are in trials to block the CCR5 receptor; some are showing promise in animal trials.

            The most famous is Maraviroc, a small molecule that binds CCR5 and stops is from binding HIV. It's sold by Pfizer and currently in use as an anti-HIV drug.

            Another interesting possibility is gene therapy. Another group has recently made CD4 T cells (one of the cell types that HIV infects) express a small molecule to block their own CCR5 receptors, which works very well. I haven't seen a paper on it, but you should also be able to use similar techniques to completely shut down CCR5 production (using virus- or plasmid-borne shRNA, for example).

            Finally, another group has managed to make rabbits produce antibodies against CCR5 receptors (Vaccine
            Volume 26, Issue 45, 23 October 2008, Pages 5752-5759). Those antibodies are able to bind to CCR5 and completely block HIV infection, which is great. Stimulating an immune response against the patient's own immune cells sound a bit dodgey to me, but my immunology isn't great: maybe there's a well-established way around this problem that I just don't know about.

            • by teklob (650327) on Sunday November 09, 2008 @07:31PM (#25698223)
              I'm only an undergrad heading towards immunology, but from what I can tell from that paper you posted, the idea is not so much to stimulate an immune response in the patient, per se.

              The immune 'response' is generated in another animal, in this case antibodies in a rabbit, to a protein resembling CCR5 receptor. This antibody is only injected back into the patient after numerous purification steps, to ensure as little cross reactivity as possible. The idea is that an antibody will bind very tightly to the exact molecule it's raised against, thereby blocking the entry of HIV. Any response to this new 'drug' antibody by the normal immune mechanisms is both unnecessary and unwanted.

              The study looks promising but since they don't know exactly what CCR5 actually looks like, they are still trying to find out what the best blocker will be. Again I have very little experience with these matters, but once this is discovered I don't see why a monoclonal antibody could be grown that would be extremely specific and likely eliminate cross reactivity.

              Any immunologists please feel free to correct me if I'm wrong.

            • by Mutatis Mutandis (921530) on Sunday November 09, 2008 @07:38PM (#25698283)

              Excellent post, but I would just like to add a few more caveats. As you probably know, but most people certainly don't, HIV occurs in a wide range of variant strains, which use either CD4 and CXCR4 or CD4 and CCR5. This is a property called "tropism" and HIV strains are classified as X4 or R5 tropic.

              But actually, from the data I have seen, few viruses exhibit a really pure tropism. There are a lot of dual-tropic X4R5 virus strains that have some flexibility to use CXCR4 or CCR5 as the opportunity offers itself; this is not surprising, as one variant must be capable of evolving into the other. Also, all patients carry diverse virus populations, because HIV is so sloppy in replicating itself, and a patient may well have 99.9% of R5-tropic viruses and 0.1% of X4-tropic viruses. (0.1% is about the limit of what can be detected with current, and very expensive, methods.)

              This is cause for concern. A treatment that blocks the replication of R5-tropic viruses may well favour the replication of X4 strains. There already are indications that this happens in some patients on maraviroc treatment. Driving a virus population to become entirely X4 tropic would probably not be advisable, as there is reason to believe that these strains do more damage. The X4-tropic HIV strains are generally associated with the late stages of infection and the development of AIDS.

              Therefore I doubt that anyone is going to advocated bone marrow transplants as a way to treat HIV. The risk is just too big, because this form of treatment is (almost) irreversible. Treatment with maravoric should always be preceded by tropism testing, and can be stopped if it doesn't work.

              Finally, 2 years of undetectable viral load in absence of ARV treatment is an impressive result, but IMHO it is still too early to call the patient cured. He may well still have proviral DNA in his cells.

        • by Pax681 (1002592) on Sunday November 09, 2008 @01:52PM (#25695485)
          IIRC i watched a TV doc about HIV immunity and how it was found. there is a link to the black death here too.

          AS it was discovered that the very same genes that help immunity from the black death are same for HIV.

          if you have none of this gene pair "switched on" then you are gonna get ill quick and die......

          if you have one of the pair on then you will go on for a few weeks THEN come down with symptoms.

          However with BOTH genes switched on you are immune but carry the black death/HIV virus. Was on the discovery channel....

          It was also apparently found that is was only ethnic Europeans who had this gene switched on... this led to some conspiracy theories about HIV/AIDS being created to be targeted at non whites.

          NEVER let it be said that a late night spliff to chill out whilst Discovery is on is a waste of your chill time!
    • by MSTCrow5429 (642744) on Sunday November 09, 2008 @01:03PM (#25695103)
      With the severely limited number of people with known immunity to HIV, and the pain of removing bone marrow, I'm wondering if more than a mere handful of people can be treated via this method.
      • by Chaos Incarnate (772793) on Sunday November 09, 2008 @01:11PM (#25695189) Homepage
        Couldn't the recipients, who will generate the new bone marrow, then be used as donors?
        • by eln (21727) on Sunday November 09, 2008 @01:19PM (#25695249) Homepage

          Right now, there's a ban on selling organs for donation in this country. However, bone marrow transplants are expensive. If the recipient could later be used as a donor, the ability to pay them for their marrow (thus allowing them to more easily pay for the original transplant) could really help move this thing along. Even if a marrow recipient is reluctant to donate his own marrow, if he had a very large medical bill and was offered money to donate, he would be much more likely to do so.

          Of course, given the limited number of naturally HIV-immune people in existence today, it would drive up the price of a transplant in the short term as they demand high prices for their marrow, but in the long run it would even out as we create more HIV-immune people.

          • by Cyberax (705495) on Sunday November 09, 2008 @01:29PM (#25695335)

            On the contrary, bone marrow transplants are the cheapest transplants.

            In essence, bone marrow transplantation is just an intravenous injection.

            • by swillden (191260) <shawn-ds@willden.org> on Sunday November 09, 2008 @04:21PM (#25696735) Homepage Journal

              On the contrary, bone marrow transplants are the cheapest transplants.

              In essence, bone marrow transplantation is just an intravenous injection.

              This is accurate, but misleading. Bone marrow transplants are cheap as transplants go, but they're still very expensive. The IV injection of the transplant is no big deal, but before it can be done the recipient's own marrow must be destroyed by chemotherapy or radiation treatments, and after the transplant the patient has to be on immunosuppresives and receive regular transfusions until the new bone marrow can establish itself. During that time, the patient also has no immune system, and must be in a hospital or other sterile environment.

              The whole process takes 1-2 months, and is far from cheap.

            • Re: (Score:3, Informative)

              by Anonymous Coward

              I can't comment on the relative cost of a BMT to other types of transplants, but to say that a BMT is just an intravenous injection is completely misleading.

              An (allogeneic) BMT is essentially the replacement of a recipient's immune system with the immune system of a donor. Before implanting the donor's immune system (which literally is an IV infusion of hemapoetic stem cells) the recipient's own immune system has to be destroyed. This is done with high-dose, whole-body radiation and high-dose chemotherap

      • by DebateG (1001165) on Sunday November 09, 2008 @01:24PM (#25695287)
        I think the end goal is to use this method for autologous stem cell transplant (when the donor is the same as the recipient) rather than allogeneic (when the donor is different). Currently, there are technologies such as small interfering RNA (siRNA) that let you suppress a specific gene through genetic engineering. They are widely used in research, although there are many hurdles before they make the transition to clinical use. It would go something like this:
        1. Draw out someone's own stem cells
        2. Permanently express the CCR5 siRNA in their stem cells by culturing them with a virus
        3. Wipe the person's bone marrow out by total body irradiation
        4. Reinfuse the altered stem cells

        The advantage of this method is that, since the stem cells are coming from your own body, there is no graft vs host disease (which is essentially like standard organ rejection, but instead the organ rejected is your entire body being rejected by the graft... you can imagine that this is very bad). Of course, you still have the problem of developing leukemia later from the total body irradiation and viral integration into an important gene. You also have a high risk of death upfront when you spend several weeks without a functional immune system when the transplant is taking. But nevertheless, it's exciting.

        • by Anpheus (908711) on Sunday November 09, 2008 @01:50PM (#25695469)

          Can you throw a little House into that? Like, say autoimmune a few times, maybe "at least it isn't lupus" or something? Amyloidosis?

        • Re: (Score:3, Informative)

          by SlashBugs (1339813)

          Depends how you choose to express the siRNA.

          Plasmids are generally pretty safe, if you pick one with decent copy-number control. Something like Epstein Barr virus' dormant plasmid would be pretty good, as it automatically keeps itself to just a few copies of itself per cell and constantly expresses a couple of RNA molecules. Just remove the viral genes and throw your shRNA in there under the same promoter... should work like a charm.

          There are also some viruses that always integrate into a specific, safe par

        • by radtea (464814) on Sunday November 09, 2008 @04:17PM (#25696697)

          Why bother wiping out the existing bone marrow?

          This isn't like leukemia, where we want to kill all the abnormal cells. The patient's existing marrow is perfectly healthy, and its presence or absence will have no effect on the ability of the donor cells to colonized the liver or where-ever it is that they typically wind up.

          So the patient shouldn't need any radiation at all. Their unmodified marrow will still produce T cells that are susceptible to the virus, but that's no big deal because the T cells from the modified marrow will be able to handle it.

          Maybe I'm missing something, but it seems at least possible that one could do this with a "marrow plant" rather than a "marrow transplant".

      • Re: (Score:3, Informative)

        by TheoMurpse (729043)

        I seem to recall a lecturer visiting my hometown's community college and giving a genetics lecture. During the lecture he claimed that the plague caused a lot of people with the CCR5 receptor that HIV attacks to die off (the plague also attacks CCR5, allegedly), thus creating a non-trivial population of northwestern Europeans who are immune to HIV.

        What's the current status of this theory? Google returns quite a few hits, but as I'm not a geneticist, and technically haven't taken a biology class in 13 years,

      • by andot (714926) on Sunday November 09, 2008 @03:12PM (#25696111)
        Bone marrow removing is not very painful. It basically chemotherapy and all needed cells are collected from blood not from bones. I have been bone marrow donor for myself. Read about it http://rarediseases.about.com/od/rarediseasesb/a/bmt05.htm [about.com]
      • by rrohbeck (944847) on Sunday November 09, 2008 @05:54PM (#25697503)

        With the severely limited number of people with known immunity to HIV, and the pain of removing bone marrow, I'm wondering if more than a mere handful of people can be treated via this method.

        It says in TFA there is a 30% mortality for bone marrow transplants, so it will never be the therapy of choice. This case is just one more piece of data indicating that the CCR5 receptor is *the* Achilles heel that makes us vulnerable to HIV, so disabling it may be the cure.

  • by Krupuk (978265) on Sunday November 09, 2008 @12:56PM (#25695023)
    Is there a way to create or replicate this bone marrow? Or will this immune donor be continually used for every AIDS patient in the world? How many natural immune donors are there? I think only a few. But still interesting.
    • by v1 (525388) on Sunday November 09, 2008 @01:03PM (#25695109) Homepage Journal

      Bone marrow replicates itself. You can keep digging it out of the same person's bone, or out of someone who receives it.

      Though I've heard this procedure is quite painful, breaking into bones to dig out (or stuff in) marrow.

      • Re: (Score:3, Interesting)

        by Tubal-Cain (1289912)
        Any hope of putting the marrow into a petri dish and growing more?
        • by DebateG (1001165) on Sunday November 09, 2008 @01:32PM (#25695351)
          Well, there are two problems with this. Firstly, hematopoietic stem cells don't last very long in culture. Lots of people are trying to figure out why, but I'm not optimistic that this problem will be solved any time soon since the cells normally exist in a complex microenvironment in the marrow that we don't really understand yet. But more importantly is the issue of MHC typing. While you need someone who has the CCR5 mutation (which is pretty rare), you also need to have someone who matches your MHC type. Think of MHC as the molecules that allow your body to identify self from non-self. The more MHC matches you have with the donor, the less chance you have of developing a life-threatening disorder called graft vs. host disease. Ideally, doctors want someone related to you, but if those people don't match, you have to do an unrelated donor search. Generally, finding a MHC match requires a large registry search that takes weeks to months to carry out, and many people, especially non-whites (due to the lack of representation of those elasticities in the bank), do not have a match.
    • by jimicus (737525) on Sunday November 09, 2008 @01:11PM (#25695179)

      Is there a way to create or replicate this bone marrow? Or will this immune donor be continually used for every AIDS patient in the world?

      It's not quite as simple as that. As I understand it, there are different bone marrow types - just like you get different blood types - and for a transplant to be successful, you want to be transferring to someone with the same type. So for every HIV+ patient, you need to find a donor who is not only of the right type, but is also naturally immune.

  • by Anonymous Coward on Sunday November 09, 2008 @12:56PM (#25695025)

    1) Be born with natural HIV immunity.
    2) Sell bone marrow to desperate people.
    3) Profit!

  • Peer review (Score:3, Interesting)

    by FeatureBug (158235) on Sunday November 09, 2008 @12:58PM (#25695051)
    The Wall Street Journal is a fine newspaper, but it is not a scientifically peer-reviewed journal. I'd wait and see what the peer review process decides about this proposed treatment. It would not be the first time that a "revolutionary" treatment has failed to prove itself in peer review.
  • by haaz (3346) on Sunday November 09, 2008 @01:17PM (#25695235) Homepage

    My late mother had a bone marrow transplant (BMT) to treat her pre-leukemic condition and try to prevent it from becoming full-bore leukemia. To do this, they blasted her whole body with radiation (sorry, don't know which frequency), which killed her existing bone marrow. They then inserted/transplanted his sister's bone marrow. Now, I am not a doctor, so I'm probably leaving out a lot of important steps here. But because of the radiation dosage, she lost her hair, a lot of weight, and the ability to keep food in her for any length of time.

    Yes, we knew this was coming. In fact, she had worked as a radiation oncologist for decades before her diagnosis with myelodysplasia. The irony abound.

    Unfortunately, either the transplant didn't take or the weakness was too much for her. She passed away on November 16, 1999. Two weeks after I'd gotten married. And some of you may remember my then-wife from what happened five months later [slashdot.org]. Yeah, life kinda sucked.

    I do want to see the HIV/AIDS pandemic curbed, and I do what I can to help people who have it live a little better. But a BMT is a major, major procedure. It's not guaranteed to be a death sentence, but it's not guaranteed to work, either. Is it worse than HIV/AIDS? That question is beyond my pay level to try and answer. I just have one story from one BMT that unfortunately did not go well. I am thankful that no one in my family has had HIV/AIDS. But I just don't know if this is the best way to deal with it once someone is infected.

  • by bjdevil66 (583941) on Sunday November 09, 2008 @01:22PM (#25695273)

    Good luck getting coverage for that kind of treatment. Probable responses: "The vat of pills you take every day is much cheaper. Claim denied." Or, "Experimental - denied."

    If this truly works on a large scale, this particular treatment will unfortunately be for the upper class only.

  • by girlintraining (1395911) on Sunday November 09, 2008 @01:37PM (#25695381)
    Most of what I've read about so-called natural immunity isn't really immunity per-se. People with immunity still carry the HIV virus; It just doesn't turn into AIDS for a long time, but in a lot of cases, eventually it overcomes the immunity. Here's an article on one such study [BBC [bbc.co.uk]].
  • by NigelTheFrog (1292406) on Sunday November 09, 2008 @01:49PM (#25695461)
    Ok, I'll admit this sounds like a neat concept for curing someone with HIV, but wouldn't you just be trading all of the consequences of having HIV/AIDS for the consequences of being a bone marrow transplant recipient? One of the most feared complications of bone marrow transplantation is graft-versus-host disease. The treatment for GVHD is...immunosuppression. So HIV patients who receive this treatment would have to face the possibility of being no better off than they were pre-treatment and potentially much, much worse (graft vs-host is a horrible condition).
  • Carrier? (Score:3, Interesting)

    by wonkavader (605434) on Sunday November 09, 2008 @01:53PM (#25695495)

    Does this or does this not still leave the recipient as an HIV carrier?

  • by Malevolent Tester (1201209) on Sunday November 09, 2008 @02:02PM (#25695573) Journal
    What relevance do sexually transmitted diseases have here?

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